Primary progressive aphasia (PPA) is a brain disease that causes a gradual and increasingly more debilitating impairment of word usage and comprehension. Although it is being recognized with increasing frequency, PPA remains underserved with respect to research and patient services. This application seeks continued funding for a project that is the centerpiece of a comprehensive PPA Research Program at Northwestern University. The goal is to make maximal use of a unique cohort that has been recruited during the first 5 years of the project and to enroll new patients for hypothesis-driven investigations of naming, word comprehension, incidental memory and sentence processing with novel tasks designed by a multidisciplinary team of investigators with a track record of close collaboration and high productivity in PPA. We believe that this type of research program can best be achieved within the structure of a multidisciplinary approach such as the one we have established for this purpose, led by researchers in neuroimaging (Dr. Emily Rogalski), neurolinguistics (Dr. Cynthia Thompson), event-related potentials (Dr. Ken Paller), neuropsychology (Dr. Sandra Weintraub), neurobehavior (Dr. Marsel Mesulam), biostatistics (Dr. Alfred Rademaker) and Magnetic Resonance physics (Dr. Todd Parrish). For the next cycle, we chose specific aims that address the four core themes of this project: subtyping and temporal evolution of PPA, mechanisms of naming and semantic distortions, characteristics of fluency and grammatical competence, and anatomical substrates of language as inferred from the distribution of peak atrophy sites in patients. Within this framework, our primary aims will be 1. To complete a longitudinal study of a select subset of current participants in order to delineat the natural course of PPA and to characterize the evolution of its initial stages (Experiment 1). 2 To clarify the mechanisms of anomia with a cross-modal ERP experiment (Experiment 2). 3. To investigate dynamic perturbations of verb and sentence processing with on-line tasks using the methodology of ERP and eye movement recording (Experiments 3 and 4). 4. To identify the anatomical basis of material- and modality-specific distortions of learning in PPA (Experiment 5). 5. To foster the continued development of the International PPA Connection (IMPPACT) website, launched through the American Recovery and Reinvestment Act (ARRA), as an international collaborative patient and resource registry (ppaconnection.org). PUBLIC HEALTH RELEVANCE: Primary progressive aphasia (PPA) is a brain disease that causes a gradual and increasingly more debilitating impairment of word usage and comprehension. Although it is being recognized with increasing frequency, PPA remains underserved with respect to research and patient services. This application seeks continued funding for a project that is the centerpiece of a comprehensive PPA Research Program at Northwestern University.